Inflammatory disease and sunlight: The vitamin D-poly (ADP-ribose) polymerase connection

Environmental factors have long been suspected to affect the pathogenesis and incidence of inflammatory diseases. Epidemiological research has demonstrated that sunlight, or rather ultraviolet radiation exposure, is one such environmental factor that can affect inflammatory diseases. Increased exposure levels of ultraviolet radiation have been shown to decrease the incidence of autoimmune diseases - including rheumatoid arthritis, Type 1 diabetes, multiple sclerosis and colitis. The immunomodulatory effects of ultraviolet radiation are mimicked by administration of vitamin D, suggesting that photosynthesized vitamin D is the mediator involved in the biological effects of sunlight. Vitamin D has a variety of roles in the body, including regulation of the immune system predominantly affecting Th1 immunity, increasing T-cell apoptosis, reducing immune-cell infiltration, decreasing cytokine/ chemokine production and suppressing proinflammatory transcription-factor activation and protein expression. Our group has provided evidence suggesting that vitamin D directly inhibits the activity of poly (ADP-ribose) polymerase, a multifunctional nuclear enzyme that also has a central role in regulating inflammation. Poly (ADP-ribose) polymerase inhibition also affects Th1 immunity in similar ways to vitamin D regulating transcription-factor activation, decreasing immune-cell infiltration and suppressing proinflammatory protein expression. Hence, inhibition of poly (ADP-ribose) polymerase by vitamin D may represent a novel mechanism for sunlight-mediated immunomodulation.